Knowledge based urban development lessons from a non-western country : the Malaysia experience

Knowledge based urban development (KBUD) is seen as a new paradigm in urban planning and development which is now being implemented across the globe in order to increase the competitiveness of cities and regions. The KBUD concept has been widely applied in western and more developed countries over the last decade, and many have been proven successful. This paper, however, aims to provide an overview of the KBUD exercise in a context of a non western country scenario—Malaysia. Literature suggests that the urban development process in non western countries is different and very much focusing on physical elements. Whether this is the case or otherwise, this paper scrutinises the project of Multimedia Super Corridor (MSC), Malaysia, which is regarded as one of the first large scale manifestations of KBUD exercise in South East Asia. Based on development policies analysis and results of the interviews with the major stakeholders, this paper investigates the application of KBUD concept within the Malaysian context by examining the development and evolution of the city of Cyberjaya—the leading intelligent city of the MSC project. In the light of the literature and case findings, the paper provides recommendations and lessons learned, on the orchestration of KBUD, for other non western cities and regions that are working hard to develop KBUD strategies, strengthening their sustainable socio-spatial policies and seeking a global recognition.

Feasibility of ranking articular cartilage conditions with non-destructive near-infrared spectroscopy with extension to the Mankin grading system

Grading osteoarthritic tissue has, until now, been a laboratory process confined to research activities. This thesis establishes a scientific protocol that extends osteoarthritic tissue ranking to surgical practice. The innovative protocol, which now incorporates the structural degeneration of collagen, enhances the traditional Modified Mankin ranking system, enabling its application to real time decision during surgery. Because it is fast and without time consuming laboratory process, it would potentially enable the cataloguing of tissues in osteoarthritic joints in all compartments of diseased joints during surgery for epistemological study and insight into the manifestation of osteoarthritis across age, gender, occupation, physical activities and race.

Pre-crash and non-crash traffic flow trends analysis on motorways

Crashes that occur on motorways contribute to a significant proportion (40-50%) of non-recurrent motorway congestions. Hence, reducing the frequency of crashes assists in addressing congestion issues (Meyer, 2008). Crash likelihood estimation studies commonly focus on traffic conditions in a short time window around the time of a crash while longer-term pre-crash traffic flow trends are neglected. In this paper we will show, through data mining techniques that a relationship between pre-crash traffic flow patterns and crash occurrence on motorways exists. We will compare them with normal traffic trends and show this knowledge has the potential to improve the accuracy of existing models and opens the path for new development approaches. The data for the analysis was extracted from records collected between 2007 and 2009 on the Shibuya and Shinjuku lines of the Tokyo Metropolitan Expressway in Japan. The dataset includes a total of 824 rear-end and sideswipe crashes that have been matched with crashes corresponding to traffic flow data using an incident detection algorithm. Traffic trends (traffic speed time series) revealed that crashes can be clustered with regards to the dominant traffic patterns prior to the crash. Using the K-Means clustering method with Euclidean distance function allowed the crashes to be clustered. Then, normal situation data was extracted based on the time distribution of crashes and were clustered to compare with the “high risk” clusters. Five major trends have been found in the clustering results for both high risk and normal conditions. The study discovered traffic regimes had differences in the speed trends. Based on these findings, crash likelihood estimation models can be fine-tuned based on the monitored traffic conditions with a sliding window of 30 minutes to increase accuracy of the results and minimize false alarms.

Driver sleepiness—Comparisons between young and older men during a monotonous afternoon simulated drive

Young men figure prominently in sleep-related road crashes. Non-driving studies show them to be particularly vulnerable to sleep loss, compared with older men. We assessed the effect of a normal night's sleep vs. prior sleep restricted to 5 h, in a counterbalanced design, on prolonged (2 h) afternoon simulated driving in 20 younger (av. 23 y) and 19 older (av. 67 y) healthy men. Driving was monitored for sleepiness related lane deviations, EEGs were recorded continuously and subjective ratings of sleepiness taken every 200 s. Following normal sleep there were no differences between groups for any measure. After sleep restriction younger drivers showed significantly more sleepiness-related deviations and greater 4–11 Hz EEG power, indicative of sleepiness. There was a near significant increase in subjective sleepiness. Correlations between the EEG and subjective measures were highly significant for both groups, indicating good self-insight into increasing sleepiness. We confirm the greater vulnerability of younger drivers to sleep loss under prolonged afternoon driving.

Planning for sustainability of non motorised public transport in a developing city

Most large cities around the world are undergoing rapid transport sector development to cater for increased urbanization. Subsequently the issues of mobility, access equity, congestion, operational safety and above all environmental sustainability are becoming increasingly crucial in transport planning and policy making. The popular response in addressing these issues has been demand management, through improvement of motorised public transport (MPT) modes (bus, train, tram) and non-motorized transport (NMT) modes (walk, bicycle); improved fuel technology. Relatively little attention has however been given to another readily available and highly sustainable component of the urban transport system, non-motorized public transport (NMPT) such as the pedicab that operates on a commercial basis and serves as an NMT taxi; and has long standing history in many Asian cities; relatively stable in existence in Latin America; and reemerging and expanding in Europe, North America and Australia. Consensus at policy level on the apparent benefits, costs and management approach for NMPT integration has often been a major transport planning problem. Within this context, this research attempts to provide a more complete analysis of the current existence rationale and possible future, or otherwise, of NMPT as a regular public transport system. The analytical process is divided into three major stages. Stage 1 reviews the status and role condition of NMPT as regular public transport on a global scale- in developing cities and developed cities. The review establishes the strong ongoing and future potential role of NMPT in major developing cities. Stage 2 narrows down the status review to a case study city of a developing country in order to facilitate deeper role review and status analysis of the mode. Dhaka, capital city of Bangladesh, has been chosen due to its magnitude of NMPT presence. The review and analysis reveals the multisectoral and dominant role of NMPT in catering for the travel need of Dhaka transport users. The review also indicates ad-hoc, disintegrated policy planning in management of NMPT and the need for a planning framework to facilitate balanced integration between NMPT and MT in future. Stage 3 develops an integrated, multimodal planning framework (IMPF), based on a four-step planning process. This includes defining the purpose and scope of the planning exercise, determining current deficiencies and preferred characteristics for the proposed IMPF, selection of suitable techniques to address the deficiencies and needs of the transport network while laying out the IMPF and finally, development of a delivery plan for the IMPF based on a selected layout technique and integration approach. The output of the exercise is a planning instrument (decision tool) that can be used to assign a road hierarchy in order to allocate appropriate traffic to appropriate network type, particularly to facilitate the operational balance between MT and NMT. The instrument is based on a partial restriction approach of motorised transport (MT) and NMT, structured on the notion of functional hierarchy approach, and distributes/prioritises MT and NMT such that functional needs of the network category is best complemented. The planning instrument based on these processes and principles offers a six-level road hierarchy with a different composition of network-governing attributes and modal priority, for the current Dhaka transport network, in order to facilitate efficient integration of NMT with MT. A case study application of the instrument on a small transport network of Dhaka also demonstrates the utility, flexibility and adoptability of the instrument in logically allocating corridors with particular positions in the road hierarchy paradigm. Although the tool is useful in enabling balanced distribution of NMPT with MT at different network levels, further investigation is required with reference to detailed modal variations, scales and locations of a network to further generalise the framework application.

The role of immunoglobulins and their transporters in urogenital Chlamydial infections

Chlamydia trachomatis infections of the male and female reproductive tracts are the world's leading sexually transmitted bacterial disease, and can lead to damaging pathology, scarring and infertility. The resolution of chlamydial infection requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Whilst cluster of differentiation (CD)4+ T cells are known to be essential in clearance of infection [1], they are also associated with immune cell infiltration, autoimmunity and infertility in the testes [2-3]. Conversely, antibodies are less associated with inflammation, are readily transported into the reproductive tracts, and can offer lumenal neutralization of chlamydiae prior to infection. Antibodies, or immunoglobulins (Ig), play a supportive role in the resolution of chlamydial infections, and this thesis sought to define the function of IgA and IgG, against a variety of chlamydial antigens expressed during the intracellular and extracellular stages of the chlamydial developmental cycle. Transport of IgA and IgG into the mucosal lumen is facilitated by receptor-mediated transcytosis yet the expression profile (under normal conditions and during urogenital chlamydial infection) of the polymeric immunoglobulin receptor (pIgR) and the neonatal Fc receptor (FcRn) remains unknown. The expression profile of pIgR and FcRn in the murine male reproductive tract was found to be polarized to the lower and upper reproductive tract tissues respectively. This demonstrates that the two receptors have a tissue tropism, which must be considered when targeting pathogens that colonize different sites. In contrast, the expression of pIgR and FcRn in the female mouse was found to be distributed in both the upper and lower reproductive tracts. When urogenitally infected with Chlamydia muridarum, both male and female reproductive tracts up-regulated expression of pIgR and down-regulated expression of FcRn. Unsurprisingly, the up-regulation of pIgR increased the concentration of IgA in the lumen. However, down-regulation of FcRn, prevented IgG uptake and led to an increase or pooling of IgG in lumenal secretions. As previous studies have identified the importance of pIgR-mediated delivery of IgA, as well as the potential of IgA to bind and neutralize intracellular pathogens, IgA against a variety of chlamydial antigens was investigated. The protection afforded by IgA against the extracellular antigen major outer membrane protein (MOMP), was found to be dependent on pIgR expression in vitro and in vivo. It was also found that in the absence of pIgR, no protection was afforded to mice previously immunized with MOMP. The protection afforded from polyclonal IgA against the intracellular chlamydial antigens; inclusion membrane protein A (IncA), inclusion membrane proteins (IncMem) and secreted chlamydial protease-like activity factor (CPAF) were produced and investigated in vitro. Antigen-specific intracellular IgA was found to bind to the respective antigen within the infected cell, but did not significantly reduce inclusion formation (p > 0.05). This suggests that whilst IgA specific for the selected antigens was transported by pIgR to the chlamydial inclusion, it was unable to prevent growth. Similarly, immunization of male mice with intracellular chlamydial antigens (IncA or IncMem), followed by depletion CD4+ T cells, and subsequent urogenital C. muridarum challenge, provided minimal pIgR-mediated protection. Wild type male mice immunized with IncA showed a 57 % reduction (p < 0.05), and mice deficient in pIgR showed a 35 % reduction (p < 0.05) in reproductive tract chlamydial burden compared to control antigen, and in the absence of CD4+ T cells. This suggests that pIgR and secretory IgA (SIgA) were playing a protective role (21 % pIgR-mediated) in unison with another antigen-specific immune mechanism (36 %). Interestingly, IgA generated during a primary respiratory C. muridarum infection did not provide a significant amount of protection to secondary urogenital C. muridarum challenge. Together, these data suggest that IgA specific for an extracellular antigen (MOMP) can play a strong protective role in chlamydial infections, and that IgA targeting intracellular antigens is also effective but dependent on pIgR expression in tissues. However, whilst not investigated here, IgA targeting and blocking other intracellular chlamydial antigens, that are more essential for replication or type III secretion, may be more efficacious in subunit vaccines. Recently, studies have demonstrated that IgG can neutralize influenza virus by trafficking IgG-bound virus to lysosomes [4]. We sought to determine if this process could also traffic chlamydial antigens for degradation by lysosomes, despite Chlamydia spp. actively inhibiting fusion with the host endocytic pathway. As observed in pIgR-mediated delivery of anti-IncA IgA, FcRn similarly transported IgG specific for IncA which bound the inclusion membrane. Interestingly, FcRn-mediated delivery of anti-IncA IgG significantly decreased inclusion formation by 36 % (p < 0.01), and induced aberrant inclusion morphology. This suggests that unlike IgA, IgG can facilitate additional host cellular responses which affect the intracellular niche of chlamydial growth. Fluorescence microscopy revealed that IgG also bound the inclusion, but unlike influenza studies, did not induce the recruitment of lysosomes. Notably, anti-IncA IgG recruited sequestosomes to the inclusion membrane, markers of the ubiquitin/proteasome pathway and major histocompatibility complex (MHC) class I loading. To determine if the protection against C. muridarum infection afforded by IncA IgG in vitro translated in vivo, wild type mice and mice deficient in functional FcRn and MHC-I, were immunized, depleted of CD4+, and urogenitally infected with C. muridarum. Unlike in pIgR-deficient mice, the protection afforded from IncA immunization was completely abrogated in mice lacking functional FcRn and MHC-I/CD8+. Thus, both anti-IncA IgA and IgG can bind the inclusion in a pIgR and FcRn-mediated manner, respectively. However, only IgG mediates a higher reduction in chlamydial infection in vitro and in vivo suggesting more than steric blocking of IncA had occurred. Unlike anti-MOMP IgA, which reduced chlamydial infection of epithelial cells and male mouse tissues, IgG was found to enhance infectivity in vitro, and in vivo. Opsonization of EBs with MOMP-IgG enhanced inclusion formation of epithelial cells in a MOMP-IgG dose-dependent and FcRn-dependent manner. When MOMP-IgG opsonized EBs were inoculated into the vagina of female mice, a small but non-significant (p > 0.05) enhancement of cervicovaginal C. muridarum shedding was observed three days post infection in mice with functional FcRn. Interestingly, infection with opsonized EBs reduced the intensity of the peak of infection (day six) but protracted the duration of infection by 60 % in wild type mice only. Infection with EBs opsonized in IgG also significantly increased (p < 0.05) hydrosalpinx formation in the oviducts and induced lymphocyte infiltration uterine horns. As MOMP is an immunodominant antigen, and is widely used in vaccines, the ability of IgG specific to extracellular chlamydial antigens to enhance infection and induce pathology needs to be considered. Together, these data suggest that immunoglobulins play a dichotomous role in chlamydial infections, and are dependent on antigen specificity, FcRn and pIgR expression. FcRn was found to be highly expressed in upper male reproductive tract, whilst pIgR was dominantly expressed in the lower reproductive tract. Conversely, female mice expressed FcRn and pIgR in both the lower and upper reproductive tracts. In response to a normal chlamydial infection, pIgR is up-regulated increasing secretory IgA release, but FcRn is down-regulated preventing IgG uptake. Similarly to other studies [5-6], we demonstrate that IgA and IgG generated during primary chlamydial infections plays a minor role in recall immunity, and that antigen-specific subunit vaccines can offer more protection. We also show that both IgA and IgG can be used to target intracellular chlamydial antigens, but that IgG is more effective. Finally, IgA against the extracellular antigen MOMP can afford protection, whist IgG plays a deleterious role by increasing infectivity and inducing damaging immunopathology. Further investigations with additional antigens or combination subunit vaccines will enhance our understanding the protection afforded by antibodies against intracellular and extracellular pathogenic antigens, and help improve the development of an efficacious chlamydial vaccine.

Storyboard augmentation of process model grammars for stakeholder communication

Process models are often used to visualize and communicate workflows to involved stakeholders. Unfortunately, process modeling notations can be complex and need specific knowledge to be understood. Storyboards, as a visual language to illustrate workflows as sequences of images, provide natural visualization features that allow for better communication, to provide insight to people from non-process modelling expert domains. This paper proposes a visualization approach using a 3D virtual world environment to visualize storyboards for business process models. A prototype was built to present its applicability via generating output with examples of five major process model patterns and two non-trivial use cases. Illustrative results for the approach show the promise of using a 3D virtual world to visualize complex process models in an unambiguous and intuitive manner.

Mainstreaming therapeutic jurisprudence and the adversarial paradigm—incommensurability and the possibility of a shared disciplinary matrix

Problem-solving courts appear to achieve outcomes that are not common in mainstream courts. There are increasing calls for the adoption of more therapeutic and problem-solving practices by mainstream judges in civil and criminal courts in a number of jurisdictions, most notably in the United States and Australia. Currently, a judge who sets out to exercise a significant therapeutic function is likely to be doing so in a specialist court or jurisdiction, outside the mainstream court system, and arguably, outside the adversarial paradigm itself. To some extent, this work is tolerated but marginalised. However, do therapeutic and problem-solving functions have the potential to help define, rather than simply complement, the role of judicial officers? The core question addressed in this thesis is whether the judicial role could evolve to be not just less adversarial, but fundamentally non-adversarial. In other words, could we see—or are we seeing—a juristic paradigm shift not just in the colloquial, casual sense of the word, but in the strong, worldview changing sense meant by Thomas Kuhn? This thesis examines the current relationship between adversarialism and therapeutic jurisprudence in the context of Kuhn’s conception of the transition from periods of ‘normal science’, through periods of anomaly and disciplinary crises to paradigm shifts. It considers whether therapeutic jurisprudence and adversarialism are incommensurable in the Kuhnian sense, and if so, what this means for the relationship between the two, and for the agenda to mainstream therapeutic jurisprudence. The thesis asserts that Kuhnian incommensurability is, in fact, a characteristic of the relationship between adversarialism and therapeutic jurisprudence, but that the possibility of a therapeutic paradigm shift in law can be reconciled with many adversarial and due process principles by relating this incommensurability to a broader disciplinary matrix.

"You’ve modelled and now what?" : Exploring determinants of process model re-use

Business process modelling as a practice and research field has received great attention over recent years. Organizations invest significantly into process modelling in terms of training, tools, capabilities and resources. The return on this investment is a function of process model re-use, which we define as the recurring use of process models to support organizational work tasks. While prior research has examined re-use as a design principle, we explore re-use as a behaviour, because evidence suggest that analysts’ re-use of process models is indeed limited. In this paper we develop a two-stage conceptualization of the key object-, behaviour- and socioorganization-centric factors explaining process model re-use behaviour. We propose a theoretical model and detail implications for its operationalization and measurement. Our study can provide significant benefits to our understanding of process modelling and process model use as key practices in analysis and design.

Application of texture analysis in tear film surface assessment based on videokeratoscopy

Purpose Videokeratoscopy images can be used for the non-invasive assessment of the tear film. In this work the applicability of an image processing technique, textural-analysis, for the assessment of the tear film in Placido disc images has been investigated. Methods In the presence of tear film thinning/break-up, the reflected pattern from the videokeratoscope is disturbed in the region of tear film disruption. Thus, the Placido pattern carries information about the stability of the underlying tear film. By characterizing the pattern regularity, the tear film quality can be inferred. In this paper, a textural features approach is used to process the Placido images. This method provides a set of texture features from which an estimate of the tear film quality can be obtained. The method is tested for the detection of dry eye in a retrospective dataset from 34 subjects (22-normal and 12-dry eye), with measurements taken under suppressed blinking conditions. Results To assess the capability of each texture-feature to discriminate dry eye from normal subjects, the receiver operating curve (ROC) was calculated and the area under the curve (AUC), specificity and sensitivity extracted. For the different features examined, the AUC value ranged from 0.77 to 0.82, while the sensitivity typically showed values above 0.9 and the specificity showed values around 0.6. Overall, the estimated ROCs indicate that the proposed technique provides good discrimination performance. Conclusions Texture analysis of videokeratoscopy images is applicable to study tear film anomalies in dry eye subjects. The proposed technique appears to have demonstrated its clinical relevance and utility.

Endothelin-1 is a novel prognostic factor in non-small cell lung cancer

Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and growth of solid tumours. This study evaluated the expression of big endothelin-1 (big ET-1), a stable precursor of ET-1, and ET-1 in non-small cell lung cancer (NSCLC). Big ET-1 expression was evaluated in paraffin-embedded tissue sections from 10 NSCLC tumours using immunohistochemistry and in situ hybridisation. The production of big ET-1 and ET-1 was studied in six established NSCLC cell lines. The plasma concentrations of big ET-1 were measured in 30 patients with proven NSCLC prior to chemotherapy by means of a sandwich enzyme-linked immunoassay and compared to levels in 20 normal controls. Big ET-1 immunostaining was detected in the cancer cells of all tumours studied. Using in situ hybridisation, tumour cell big ET-1 mRNA expression was demonstrated in all samples. All six NSCLC cell lines expressed ET-1, with big ET-1 being detected in three. The median big ET-1 plasma level in patients with NSCLC was 5.4 pg/mL (range 0-22.7 pg/mL) and was significantly elevated compared to median big ET-1 plasma levels in controls, 2.1 pg/mL (1.2-13.4 pg/mL) (p=0.0001). Furthermore, patients with plasma big ET-1 levels above the normal range (upper tertile) had a worse outcome (p=0.01). In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists such as Atrasentan indicates that ET-1 may be a therapeutic target in NSCLC. © 2004 Wichtig Editore.

Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer

Background: Angiogenesis may play a role in the pathogenesis of Non-Small Cell Lung cancer (NSCLC). The CXC (ELR+) chemokine family are powerful promoters of the angiogenic response. Methods: The expression of the CXC (ELR+) family members (CXCL1-3/GROα-γ, CXCL8/IL-8, CXCR1/2) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of these chemokines was examined in normal bronchial epithelial and NSCLC cell lines. Results: Overall, expression of the chemokine ligands (CXCL1, 2, 8) and their receptors (CXCR1/2) were down regulated in tumour samples compared with normal, with the exception of CXCL3. CXCL8 and CXCR1/2 were found to be epigenetically regulated by histone post-translational modifications. Recombinant CXCL8 did not stimulate cell growth in either a normal bronchial epithelial or a squamous carcinoma cell line (SKMES-1). However, an increase was observed at 72 hours post treatment in an adenocarcinoma cell line. Conclusions: CXC (ELR+) chemokines are dysregulated in NSCLC. The balance of these chemokines may be critical in the tumour microenvironment and requires further elucidation. It remains to be seen if epigenetic targeting of these pathways is a viable therapeutic option in lung cancer treatment. © 2011 Baird et al.

Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer

Background: Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease. Methods: TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB 2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results: TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB 2levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC. © 2011 Cathcart et al; licensee BioMed Central Ltd.

Angiogenesis and non-small cell lung cancer

Lung cancer is the commonest cause of cancer death in the western world. Recent evidence suggests that angiogenesis is related to poor prognosis in many solid tumours including non-small cell lung cancer. Angiogenesis is controlled by a complex interaction between growth and apoptotic factors, proteases and adhesion molecules. The angiogenic process may prove a target for novel therapies such as matrix metalloproteinase inhibitors, growth factor antisense RNA, growth factor receptor antagonists and naturally occurring antiangiogenic peptides. These agents may be used alone or in combination with traditional chemotherapy, radiotherapy and surgery. (C) 2000 Elsevier Science Ireland Ltd.